Year: 2016
Type: article
Abstract: The easy accessibility of skin makes it an excellent target for gene therapy applications. Gene electrotransfer (GET) of skin is a simple, direct, in vivo method to deliver genes for therapy and can be accomplished in a minimally invasive way. This approach has been tested in several animal models with varying skin thickness and delivery of plasmid DNA with GET resulted in significantly increased expression levels. Previously, we developed electrode arrays specifically for skin-based applications and designed applicators that can be easily applied and expanded. The limitations that we have encountered with our new designs are related to the depth of penetration of expression and occasionally cellular or tissue damage due to the required high applied voltage. GET requires a balance between efficient delivery and the maintenance of cell viability. In this current study, we have evaluated the addition of externally applied thermal energy to GET protocols to enhance delivery without increasing the applied voltage. We have determined both in vitro and in vivo that elevating the tissue temperature to between 42-45 0C was sufficient to enhance delivery when combined with GET. Administering GET to tissue with elevated temperature resulted in 5-8 fold higher expression compared to delivery with GET alone (ambient temperature). In addition, expression was obtained in the deep dermis and muscle utilizing a surface electrode. This deeper penetration was not consistently obtained when GET was used without a thermal component. Current work is evaluating approaches to achieve more uniform heat distribution within the tissue and to potentially elevate temperatures in specific areas of tissue in order to target gene expression. GET is a powerful tool that allows for manipulation of expression levels and kinetics. Adjusting the delivery parameters enables maximum control of the expression profile enhancing the potential for a successful therapeutic outcome. The addition of the thermal component allows further control of delivery and reduces the potential for cellular damage.
Source: Molecular Therapy
Institution: Old Dominion University
Language: English
Subfield: Biotechnology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
OpenAlex ID: W2565853287